KRT84

Summary

KRT84 (keratin 84, HGNC:6461) is a protein-coding gene on chromosome 12q13.13, encoding Keratin, type II cuticular Hb4 (Q9NSB2).

The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related subfamily includes KRTHB2, KRTHB4, and KRTHB5. All hair keratins are expressed in the hair follicle; this hair keratin is contained primarily in the filiform tongue papilla, among other hair keratins.

Source: NCBI Gene 3890 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 126 total
• MANE Select transcript: NM_033045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6461
Approved symbol	KRT84
Name	keratin 84
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	Hb-4
Ensembl gene	ENSG00000161849
Ensembl biotype	protein_coding
OMIM	602766
Entrez	3890

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000257951

RefSeq mRNA: 1 — MANE Select: NM_033045 NM_033045

CCDS: CCDS8825

Canonical transcript exons

ENST00000257951 — 9 exons

Exon	Start	End
ENSE00000919885	52377812	52378380
ENSE00000919886	52379876	52379907
ENSE00000919887	52380363	52380583
ENSE00000919888	52381080	52381205
ENSE00000919890	52382437	52382532
ENSE00000919892	52383590	52383798
ENSE00000919893	52385040	52385652
ENSE00001695106	52381361	52381525
ENSE00001738900	52383005	52383065

Expression profiles

Bgee: expression breadth broad, 21 present calls, max score 42.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6548 / max 815.9880, expressed in 8 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131027	0.6548	8

Top tissues by expression

122 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	42.46	gold quality
tonsil	UBERON:0002372	40.24	gold quality
skin of abdomen	UBERON:0001416	39.46	gold quality
prefrontal cortex	UBERON:0000451	38.63	silver quality
zone of skin	UBERON:0000014	37.67	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skin of leg	UBERON:0001511	36.53	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.54	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.74	gold quality
frontal cortex	UBERON:0001870	34.73	silver quality
vagina	UBERON:0000996	33.31	gold quality
superior frontal gyrus	UBERON:0002661	32.62	gold quality
muscle tissue	UBERON:0002385	32.06	gold quality
cerebral cortex	UBERON:0000956	31.89	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	31.08	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
anterior cingulate cortex	UBERON:0009835	30.09	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
urinary bladder	UBERON:0001255	29.55	gold quality
monocyte	CL:0000576	29.54	gold quality
leukocyte	CL:0000738	29.36	gold quality
liver	UBERON:0002107	29.25	gold quality
right frontal lobe	UBERON:0002810	29.17	gold quality
ectocervix	UBERON:0012249	28.60	gold quality
spleen	UBERON:0002106	28.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting KRT84, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-22-5P	97.67	68.92	1355

Literature-anchored findings (GeneRIF, showing 1)

• KRT84 is a potential tumor suppressor and good prognosis signature of oral squamous cell carcinoma. (PMID:32181476)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt84	ENSMUSG00000044294
rattus_norvegicus	Krt84	ENSRNOG00000008819

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Keratin, type II cuticular Hb4 — Q9NSB2 (reviewed: Q9NSB2)

Alternative names: Keratin-84, Type II hair keratin Hb4, Type-II keratin Kb24

All UniProt accessions (1): Q9NSB2

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Heterotetramer of two type I and two type II keratins.

Tissue specificity. Expressed in the hair follicles.

Miscellaneous. There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic).

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_149034* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003054	Keratin_II	Family
IPR018039	IF_conserved	Conserved_site
IPR032444	Keratin_2_head	Domain
IPR039008	IF_rod_dom	Domain

Pfam: PF00038, PF16208

UniProt features (19 total): region of interest 7, sequence variant 5, sequence conflict 5, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSB2-F1	68.52	0.45

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-6809371	Formation of the cornified envelope
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 84 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_APPENDAGE_DEVELOPMENT, HFH8_01, FOXJ2_01, GOBP_MOLTING_CYCLE, GOBP_EPIDERMIS_DEVELOPMENT, AFP1_Q6, GOBP_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, FOXJ2_02, GOBP_KERATINIZATION

GO Biological Process (5): hair follicle development (GO:0001942), keratinization (GO:0031424), nail development (GO:0035878), intermediate filament organization (GO:0045109), regulation of keratinocyte differentiation (GO:0045616)

GO Molecular Function (2): structural constituent of cytoskeleton (GO:0005200), structural constituent of skin epidermis (GO:0030280)

GO Cellular Component (5): cytosol (GO:0005829), keratin filament (GO:0045095), extracellular exosome (GO:0070062), intermediate filament (GO:0005882), intermediate filament cytoskeleton (GO:0045111)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Biology	1
Keratinization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	2
keratinocyte differentiation	2
structural molecule activity	2
cytoskeleton	2
hair cycle process	1
skin epidermis development	1
multicellular organismal process	1
limb development	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
regulation of epidermal cell differentiation	1
cytoskeleton organization	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
extracellular vesicle	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT84	KRTAP3-1	Q9BYR8	520
KRT84	OR6X1	Q8NH79	506
KRT84	KRTAP13-1	Q8IUC0	500
KRT84	HOXC13	P31276	489
KRT84	DSG4	Q86SJ6	453
KRT84	SELENBP1	Q13228	426
KRT84	AKR1B10	O60218	424
KRT84	MEPCE	Q7L2J0	424
KRT84	LY6D	Q14210	413
KRT84	SPRR4	Q96PI1	398
KRT84	KRTAP19-7	Q3SYF9	392
KRT84	PRSS53	Q2L4Q9	388
KRT84	STARD9	Q9P2P6	383
KRT84	PRR9	Q5T870	375
KRT84	OR13J1	Q8NGT2	375

IntAct

14 interactions, top by confidence:

A	B	Type	Score
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
STARD8	JPH1	psi-mi:“MI:0914”(association)	0.530
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
SLX1A	PSMD11	psi-mi:“MI:0914”(association)	0.350
USP37	ALB	psi-mi:“MI:0914”(association)	0.350
KATNIP		psi-mi:“MI:0914”(association)	0.350
CFTR	POTEF	psi-mi:“MI:0914”(association)	0.350
SULF2	IGHA1	psi-mi:“MI:0914”(association)	0.350
ARMC9	PRMT5	psi-mi:“MI:0914”(association)	0.350
NRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
FHIP2A	MED19	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (51): KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-RNA), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), KRT84 (Affinity Capture-MS)

ESM2 similar proteins: A0JND2, A3KN27, A5A6N0, A6BLY7, A6H712, A6QNX5, A7YWK3, E1AB55, P07744, P08729, P19013, P25691, Q0P5J4, Q0P5J6, Q0P5J7, Q0VBK2, Q148H5, Q148H6, Q148H7, Q148H8, Q14CN4, Q3SY84, Q5XKE5, Q64291, Q6IFW8, Q6IFZ9, Q6IG00, Q6IG01, Q6IG03, Q6IG04, Q6IME9, Q6IMF0, Q6IMF1, Q6KB66, Q6NXH9, Q6R649, Q7RTS7, Q7Z3Y7, Q7Z3Y9, Q7Z794

Diamond homologs: A0A8C0N8E3, A0JND2, A3KN27, A4FUZ0, A5A6M6, A5A6M8, A5A6N0, A6QNX5, A6QQJ3, A7YWK3, E1AB55, O43790, O93532, O95678, P02538, P04104, P04259, P04264, P04265, P04266, P05786, P05787, P07744, P08670, P08729, P08776, P11679, P12035, P13647, P15241, P15331, P16878, P18520, P19013, P21807, P25691, P35908, P41219, P48616, P48668

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

126 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1088 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52379874:A:AC	donor_gain	1.0000
12:52379875:C:CC	donor_gain	1.0000
12:52380355:GTACT:G	donor_loss	1.0000
12:52380357:ACT:A	donor_loss	1.0000
12:52380359:TCA:T	donor_loss	1.0000
12:52380360:CA:C	donor_loss	1.0000
12:52380361:A:AC	donor_gain	1.0000
12:52380361:A:T	donor_loss	1.0000
12:52380361:AC:A	donor_gain	1.0000
12:52380361:ACCGG:A	donor_gain	1.0000
12:52380362:C:CG	donor_gain	1.0000
12:52380362:CC:C	donor_gain	1.0000
12:52380362:CCGG:C	donor_gain	1.0000
12:52380362:CCGGC:C	donor_gain	1.0000
12:52380580:CACG:C	acceptor_gain	1.0000
12:52380582:CG:C	acceptor_gain	1.0000
12:52380584:C:CC	acceptor_gain	1.0000
12:52381075:CCCA:C	donor_loss	1.0000
12:52381076:CCACC:C	donor_loss	1.0000
12:52381077:CACCT:C	donor_loss	1.0000
12:52381078:A:C	donor_loss	1.0000
12:52381079:C:CT	donor_loss	1.0000
12:52381105:G:GA	donor_gain	1.0000
12:52381110:AAG:A	donor_gain	1.0000
12:52381201:TCATA:T	acceptor_gain	1.0000
12:52381202:CATA:C	acceptor_gain	1.0000
12:52381202:CATAC:C	acceptor_gain	1.0000
12:52381203:ATA:A	acceptor_gain	1.0000
12:52381204:TA:T	acceptor_gain	1.0000
12:52381206:C:CC	acceptor_gain	1.0000

AlphaMissense

3920 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52385058:A:C	F176L	0.987
12:52385058:A:T	F176L	0.987
12:52385060:A:G	F176L	0.987
12:52383008:C:A	K271N	0.977
12:52383008:C:G	K271N	0.977
12:52385059:A:C	F176C	0.964
12:52385059:A:G	F176S	0.963
12:52383779:T:G	Q189P	0.957
12:52385068:T:A	N173I	0.954
12:52383020:A:C	F267L	0.953
12:52383020:A:T	F267L	0.953
12:52383022:A:G	F267L	0.953
12:52380422:C:A	K455N	0.950
12:52380422:C:G	K455N	0.950
12:52383794:C:G	R184P	0.950
12:52385067:G:C	N173K	0.949
12:52385067:G:T	N173K	0.949
12:52383782:T:G	Q188P	0.939
12:52385049:G:C	F179L	0.939
12:52385049:G:T	F179L	0.939
12:52385051:A:G	F179L	0.939
12:52385071:A:G	L172P	0.938
12:52380384:A:G	L468P	0.932
12:52383784:C:A	E187D	0.926
12:52383784:C:G	E187D	0.926
12:52381384:C:G	A352P	0.925
12:52382458:A:C	F297L	0.925
12:52382458:A:T	F297L	0.925
12:52382460:A:G	F297L	0.925
12:52385056:G:T	A177D	0.925

dbSNP variants (sampled 300 via entrez): RS1000421639 (12:52379415 T>A), RS1001134522 (12:52379676 C>A), RS1001315457 (12:52380224 C>A), RS1001688382 (12:52380752 ATGGGGTAGGGCAT>A), RS1002026991 (12:52379588 G>C), RS1002566716 (12:52383876 A>G), RS1002637652 (12:52385274 AC>A,ACC), RS1002704386 (12:52377879 G>T), RS1002720110 (12:52388902 G>A,T), RS1002819919 (12:52380278 A>G), RS1002898668 (12:52387697 T>G), RS1002939648 (12:52388677 G>T), RS1003022482 (12:52382720 G>A,T), RS1003195648 (12:52383703 G>A), RS1003232261 (12:52386677 T>C)

Disease associations

OMIM: gene MIM:602766 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases expression	1
Phenolsulfonphthalein	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.